Aggregation of amyloid proteins is associated with a number of diseases, including Alzheimer's disease, Parkinson's disease, and type II diabetes. Although there is still a debate on whether the aggregation is the symptoms or the cause of the diseases, a better understanding of amyloid aggregation at the molecular level can provide crucial information for steering strategies for drug development in fighting amyloid diseases. Membrane is known to play a crucial role in amyloid aggregation. Recent studies have shown that lipid molecules are reliable biomarkers for detecting amyloid diseases before the onset of symptoms. Moreover, interactions with membrane can catalyze amyloid aggregation and the aggregation product formed at the early stages can disrupt cell membrane and cause cytotoxicity. Thus, it is significant to understand amyloid aggregation on membrane surfaces. However, most previous molecular studies of amyloid aggregation were carried out in solution phase. Hence, there is a large gap of knowledge about the role of membrane surfaces in amyloid aggregation. Nonetheless, bridging the gap requires surface-specific physical methods that can monitor conformational changes in amyloid proteins upon interactions with membrane surfaces in situ and in real time. The challenge is the need of surface-specificity that can eliminate interference of signals from proteins in solution phase and from water solvent such that surface information can be preserved. For the last 5 years, we have developed surface-specific chiral sum frequency generation (cSFG) vibrational spectroscopy into a new approach for label-free characterization of protein secondary structures at interfaces. We successfully used cSFG to study human islet amyloid polypeptide (hIAPP) that is associated with type II diabetes. We monitored the kinetics of the misfolding of hIAPP from disordered structures to ?-helices and then ?-sheets upon interactions with lipid surfaces. Also, we preformed ab initio calculations for analyzing cSFG spectra and obtained molecular orientation of the ?-sheet aggregates of hIAPP on membrane surfaces. Here, we propose to use cSFG method combined with other surface chemistry methods to study the aggregation of hIAPP in early stages on membrane surfaces. We will focus on the effects of (1) lipid compositions, particularly those biomarker lipids proven to be useful for detecting amyloid diseases, (2) drug candidates, including small molecules and peptides, that are known to inhibit fibril formation, and (3) the S20G mutant of hIAPP, the only mutant associated with early onset of type II diabetes. We will measure the rates of conformational changes of hIAPP and the mutant on lipid membranes with various levels of biomarker lipids and addition of the drug candidates. The results will offer mechanistic understanding of amyloid aggregation in the early stages on the membrane surfaces, providing insights into the role of amyloid aggregation in pathogenesis of the diseases and offering guidance in prioritizing resource in amyloid research.